The research project involves the creation of a novel class of glycoconjugates for the prevention of HIV entry. The proposed research describes the synthetic routes and methods utilized to prepare glycoconjugate libraries designed as HIV entry inhibitors. The design of the target compound is based on the gp120 recognition region of cellular receptor CD4. An oligosaccharide scaffold will be utilized to place critical amino acid side-chains in positions that should prove favorable for binding to gp120. The goals to be met with this project are two-fold. First, the efficient synthesis of glycoconjugates on solid-support will allow for the timely production of a variety of gylcoconjugates. Secondly, the screening of these glycoconjugate libraries for binding to gp120 will be investigated. The research will be divided into three portions: 1) The initial step will be to prepare a glycoconjugate lead compound via solid-phase synthesis to validate the synthetic methods. 2) The systematic modification of the amino-acid side-chains will reveal the importance of a variety of factors, such as stereochemistry and functional group tolerance. 3) The information gained from the first two portions will allow for libraries to be efficiently prepared based on structure activity relationships. [unreadable] [unreadable] Public Health Relevance: Acquired Immune Deficiency Syndrome (AIDS) is the leading cause of death globally. AIDS is caused by the retrovirus HIV. While preventing the spread of HIV is of great importance, the treatment of HIV infection is also significant as proper treatment can retard the progression of AIDS. While there are numerous treatments currently in use, the production of new HIV therapies remains a valuable weapon in the battle against HIV. [unreadable] [unreadable] [unreadable]